Concerns over a terrorist radionuclide threat have prompted the need for improved methods ofremoving internally deposited radionuclides. Methods for radionuclide removal include chelation therapy, blocking uptake, and accelerating the clearance of ingested or inhaled radionuclidesfrom the body. Natural receptors, which exist in diverse physicochemical forms, often possess versatile chelation propertiesdue to the presence of multiple functional groups, making them capable of binding dissimilar metal ions via multiple chelation mechanisms. The hypothesis of the proposed researchis that the natural chelator chitosan is a safe and effective decorporation agent for a wide range of radionuclides. The Specific Aims designedto test this hypothesis will provide a comprehensive assessment of decorporation efficacy and toxicity ofchitosan materials in vitro and in vivo. The initial Aim will include in vitro studies to evaluate the affinity ofchitosan materials for radionuclides under physiological conditions, including chemically modifying chitosan for Cs- 137 binding, in order to identify the most promising candidates for subsequent studies. The secondAim will evaluate the in vivo toxicity of candidate chitosan derivatives in F344 rats in order to refine the most promising cnadidates, and the final Aim will evaluate the in vivo decorporation efficacy of candidate chitosan derivatives for exposure to radionuclides in order to develop sufficient pharmacokinetic data toestimate utility in human populations using biokinetic dosimetric models. The primary benefit of this researchis the rapid development of non-toxic, naturally effective decorporationagents for a wide range of radionuclides. These agents could be already available on the market, or could be easily modified and produced in large quantities. The non-toxic nature of such agents, along with their current use in the medical and pharmaceutical fields will allow these agents to be safely distributed to the general public for both medical /mitigation and prophylactic purposes rapidly in the event of a nuclear emergency.